The alphavirus group consists of about 20 viruses, many of which are important human veterinary pathogens. We will continue our study of the molecular biology of alphavirus replication in several ways. We have constructed a complete cloned DNA copy of the Sindbis virus RNA and are developing techniques to rapidly construct cloned DNA copies inserted next to promoter sequences or restriction sites. We will attempt to obtain infectious RNA from such cloned copies which would in turn allow numerous experiments which probe the replication strategy of this virus. We have completely sequenced the genome of Sindbis virus, 11703 nucleotides in length, and will map all of the proteins encoded in this RNA to the RNA nucleotide sequence. We will also continue comparative studies of alphaviruses to study their evolution. We have initiated studies of a second group of Togaviruses, the flaviviruses, which contain about 60 members of which many are important human pathogens. We intend to sequence the structural proteins of the vaccine strain of yellow fever virus by a combination of nucleotide sequencing and protein sequencing in order to probe the replication strategy of these viruses and to obtain comparative sequence data on several flaviviruses to study their evolution. Both alphaviruses and flaviviruses alternate in nature between growth in arthropod vectors (mosquitoes or ticks) and growth in vertebrates and studies of strain divergences are of particular interest.